Factors governing helical preference of peptides containing multiple alpha,alpha-dialkyl amino acids.
The presence of multiple alpha,alpha-dialkyl amino acids such as alpha-methylalanine (alpha-aminoisobutyric acid, Aib) leads to predominantly helical structures, either with alpha-helical or 3(10)-helical hydrogen bonding patterns. The crystal structure of emerimicin-(1-9) benzyl ester (Ac-Phe-Aib-Aib-Aib-Val-Gly-Leu-Aib-Aib-OBzl) reported here shows essentially pure alpha-helical character, whereas other similar compounds show predominantly 3(10)-helical structures. The factors that govern helical preference include the inherent relative stability of the alpha-helix compared with the 3(10)-helix, the extra hydrogen bond seen with 3(10)-helices, and the enhanced electrostatic dipolar interaction of the 3(10)-helix when packed in a crystalline lattice. The balance of these forces, when combined with the steric requirements of the amino acid side chains, determines the relative stability of the two helical conformations under a given set of experimental conditions.
Marshall
G R
GR
Department of Pharmacology, Washington University School of Medicine, Saint Louis, MO 63110.
Hodgkin
E E
EE
Langs
D A
DA
Smith
G D
GD
Zabrocki
J
J
Leplawy
M T
MT
D000595:Amino Acid Sequence; D000613:Aminobutyrates; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009842:Oligopeptides; D010446:Peptide Fragments; D011487:Protein Conformation
D000613:Aminobutyrates; D009842:Oligopeptides; D010446:Peptide Fragments; C062261:emerimicin (1-9) benzyl ester; C012223:alpha-aminobutyric acid